Osimertinib In EGFR Mutant Lung Cancer

Exclusion Criteria

• •Prior or ongoing treatment with any of the following:
• •* EGFR targeted therapy (TKI or antibody) or any other targeted therapies targeting the ERBB family except for subjects receiving first line osimertinib during the first three months of therapy.
• •* Any cytotoxic chemotherapy, investigational agents, immunotherapy or anticancer drugs for the treatment of metastatic NSCLC
• •* Note: Patients who have completed adjuvant or neo-adjuvant chemotherapy \> 6 months ago are considered treatment naïve
• •Prior radiotherapy, including CNS radiation, within 2 weeks of the first dose of study treatment.
• •Uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic untreated brain metastases are eligible. Patients with treated CNS disease will be allowed to enroll provided they have asymptomatic clinically confirmed stable disease with ≥2 weeks since definitive CNS therapy (radiation or surgery) and ≥2 weeks without systemic steroids. Patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry.
• •History of allergic reactions attributed to compounds, or any of its excipients, of similar chemical or biologic composition to osimertinib.
• •Patients currently receiving and unable to stop using medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4. The full list of medications that would make a patient ineligible are provided in Appendix B, along with indicated washout times.
• •Any unresolved toxicities from prior therapy, including commercial osimertinib, greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment.
• •Malignancies within the past 3 years excluding adequately treated basal or squamous cell carcinomas of the skin without local or distant metastases.
• •Refractory nausea and vomiting, chronic gastrointestinal diseases, previous significant bowel resection, or any process that compromises the ability to swallow or absorb oral medication
• •Significant medical history or unstable medical comorbidities, including:
• •* heart disease including congestive heart failure (NYHA Grade II or greater); unstable angina; prior myocardial infarction (NSTEMI or STEMI) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of \>150 mm Hg or diastolic blood pressure of \>100 mm Hg while on antihypertensive medication
• •* any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250msec, have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
• •* any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval and cause Torsades de Pointes and listed in Appendix B that a patient is unable to stop
• •* past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• •* active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
• •* known active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Screening for chronic conditions is not required. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib.
• •* cardiac ejection fraction of \< 45%
• •* Any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
• •Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M. Note: testing is not required for study entry.
• •Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry. Women of child-bearing potential must have a negative pregnancy test prior to start of dosing.
• •Pregnant women are excluded from this study because the effects of osimertinib on the development of the fetus are unknown, and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with osimertinib, breastfeeding should be discontinued if the mother is treated with osimertinib.